目的研究NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体及其下游炎症因子在慢性阻塞性肺疾病(简称慢阻肺)患者和健康人之间表达的差异,揭示NLRP3炎性小体在慢阻肺发病机制中的可能作用。方法选取2016年11月至2017年5月住院的40例慢阻...目的研究NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体及其下游炎症因子在慢性阻塞性肺疾病(简称慢阻肺)患者和健康人之间表达的差异,揭示NLRP3炎性小体在慢阻肺发病机制中的可能作用。方法选取2016年11月至2017年5月住院的40例慢阻肺患者纳入急性加重期组,其经过治疗进入稳定期后纳入稳定期组,选取40例健康体检者纳入对照组。采集各组一般资料和外周血,荧光定量PCR法测定外周血单个核细胞中NLRP3 m RNA水平,酶联免疫法检测血浆白细胞介素-18(IL-18)和白细胞介素-1β(IL-1β)水平。结果急性加重期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于稳定期组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml比1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml,P<0.05]。急性加重期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于对照组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml比1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。稳定期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于对照组[1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml比1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。急性加重期组血浆IL-18水平和白细胞计数、中性粒细胞百分比呈正相关(r=0.372,P<0.05;r=0.386,P<0.05);急性加重期组NLRP3 m RNA表达量和稳定期组NLRP3 m RNA表达量均与CAT评分正相关(r=0.387,P<0.05;r=0.399,P<0.05)。结论 NLRP3炎性小体参与慢阻肺患者的机体炎症反应。展开更多
Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects c...Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice, However, the inflammasome sensor absent in melanoma 2 （AIM2） protects against coiorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways, Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined, Here we show that the AIM2 inflammasome has a protective role in the intestine, During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein （IL-22BP） in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides （AMPs） Reg3β and Reg3γ, which promotes dysbiosis-linked colitis, During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2^-/- mice promotes excessive IL-22 production and elevated STAT3 activation, Aim2^-/- mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression, This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2^-/- mice to colorectal cancer, Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.展开更多
文摘目的研究NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体及其下游炎症因子在慢性阻塞性肺疾病(简称慢阻肺)患者和健康人之间表达的差异,揭示NLRP3炎性小体在慢阻肺发病机制中的可能作用。方法选取2016年11月至2017年5月住院的40例慢阻肺患者纳入急性加重期组,其经过治疗进入稳定期后纳入稳定期组,选取40例健康体检者纳入对照组。采集各组一般资料和外周血,荧光定量PCR法测定外周血单个核细胞中NLRP3 m RNA水平,酶联免疫法检测血浆白细胞介素-18(IL-18)和白细胞介素-1β(IL-1β)水平。结果急性加重期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于稳定期组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml比1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml,P<0.05]。急性加重期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于对照组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml比1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。稳定期组慢阻肺患者的NLRP3 m RNA、IL-18和IL-1β水平显著高于对照组[1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml比1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。急性加重期组血浆IL-18水平和白细胞计数、中性粒细胞百分比呈正相关(r=0.372,P<0.05;r=0.386,P<0.05);急性加重期组NLRP3 m RNA表达量和稳定期组NLRP3 m RNA表达量均与CAT评分正相关(r=0.387,P<0.05;r=0.399,P<0.05)。结论 NLRP3炎性小体参与慢阻肺患者的机体炎症反应。
文摘Inflammasomes are important for maintaining intestinal homeostasis, and dysbiosis contributes to the pathology of inflammatory bowel disease （IBD） and increases the risk for colorectal cancer, Inflammasome defects contribute to chronic intestinal inflammation and increase the susceptibility to colitis in mice, However, the inflammasome sensor absent in melanoma 2 （AIM2） protects against coiorectal cancer in an inflammasome-independent manner through DNA-dependent protein kinase and Akt pathways, Yet, the roles of the AIM2 inflammasome in IBD and the early phases of colorectal cancer remain ill-defined, Here we show that the AIM2 inflammasome has a protective role in the intestine, During steady state, Aim2 deletion results in the loss of IL-18 secretion, suppression of the IL-22 binding protein （IL-22BP） in intestinal epithelial cells and consequent loss of the STAT3-dependent antimicrobial peptides （AMPs） Reg3β and Reg3γ, which promotes dysbiosis-linked colitis, During dextran sulfate sodium-induced colitis, a dysfunctional IL-18/IL-22BP pathway in Aim2^-/- mice promotes excessive IL-22 production and elevated STAT3 activation, Aim2^-/- mice further exhibit sustained STAT3 and Akt activation during the resolution of colitis fueled by enhanced Reg3b and Reg3g expression, This self-perpetuating mechanism promotes proliferation of intestinal crypt cells and likely contributes to the recently described increase in susceptibility of Aim2^-/- mice to colorectal cancer, Collectively, our results demonstrate a central role for the AIM2 inflammasome in preventing dysbiosis and intestinal inflammation through regulation of the IL-18/IL-22BP/IL-22 and STAT3 pathway and expression of select AMPs.
